Rosuvastatin dose-dependently improves flow-mediated dilation, but reduces adiponectin levels and insulin sensitivity in hypercholesterolemic patients

Abstract

Background: Genetic analysis from patients participated in the randomized trials reported that the increased risk of type 2 diabetes noted with statins is at least partially explained by HMG-coenzyme A reductase inhibition. We investigated vascular and metabolic phenotypes of different dosages of rosuvastatin in hypercholesterolemic patients. Methods: A randomized, single-blind, placebo-controlled, parallel study was conducted in 48 patients on placebo, and in 47, 48, and 47 patients given daily rosuvastatin 5, 10, and 20 mg, respectively during a 2 month treatment period. Results: Rosuvastatin 5, 10, and 20 mg improved flow-mediated dilation (34, 40, and 46%) after 2 months therapy when compared with baseline (P < 0.001 by paired t-test) and when compared with placebo (P < 0.001 by ANOVA). Rosuvastatin 5,10, and 20 mg dose-dependently and significantly increased insulin (mean % changes; 19, 29, and 31%, respectively) and glycated hemoglobin levels (mean % changes; 2, 2, and 3%, respectively), and decreased adiponectin levels (mean % changes; 3, 9, and 14%, respectively) and insulin sensitivity (mean % changes; 2, 3, and 4%, respectively) after 2 months therapy when compared with baseline (all P < 0.05 by paired t-test). These effects with rosuvastatin 5, 10, and 20 mg were significant when compared with placebo (P= 0.006 for insulin, P= 0.012 for glycated hemoglobin, P= 0.007 for adiponectin, and P= 0.002 for insulin sensitivity by ANOVA). Conclusions: Despite beneficial reductions in LDL cholesterol and improvement of flow-mediated dilation, rosuvastatin dose-dependently and significantly resulted in decreasing insulin sensitivity and increasing ambient glycemia by reducing adiponectin levels and increasing insulin levels in hypercholesterolemic patients. (C) 2016 Elsevier Ireland Ltd. All rights reserved.